Much of pediatric hypertension occurs in the newborn, especially in the neonatal intensive care unit.1'4 The diagnosis of hypertension is not difficult with the advent of new techniques for blood pressure measurement in the neonate, the establishment of normal blood pressure values in low birthweight and very low birthweight infants, and increased physician awareness of neonatal hypertension and its causes. This article discusses some of the diagnostic pitfalls confronting the physician and offers useful guidelines in the evaluation and management of the hypertensive neonate.
BLOOD PRESSURE MEASUREMENT
At any age, accurate measurement of blood pressure is essential for the diagnosis of hypertension. The most commonly used techniques for measurements of blood pressure in infants are direct intra-arterial recordings, Doppler ultrasound, oscillometry, «and palpation. Direct recordings are usually obtained using an indwelling catheter passed into the abdominal aorta through an umbilical artery. Although direct measurements are highly accurate, they are often temporary readings obtained when an umbilical artery catheter is in place for other clinical reasons and may be associated with significant catheter sequelae, such as infection, vasospasm, and thrombosis.2 Doppler and oscillometry are safe, noninvasive, and accurate techniques.5,6 Oscillometry is routinely used in many nurseries to provide on-line blood pressure monitoring.
No matter which method is employed for measurement, blood pressure values will be affected by birthweight,7 postnatal age,8 level of activity, and cuff size. Failure to recognize these factors results in under- or overdiagnosis and may lead to unnecessary studies and therapy. The bladder width of the cuff should cover at least two thirds of the upper arm or thigh. Alternately, the ratio of cuff width to arm circumference should be between 0.44 and 0.55. A small cuff will lead to erroneously high blood pressure values. Crying,7 agitation, pain, and endotracheal suctioning may increase blood pressure substantially.
Both systolic and diastolic blood pressure rise with birthweight7 and age,8 with the most marked changes occurring during the first week of life. Blood pressure rises 1 to 2 mmHg per day during the first week of life and 1 to 2 mmHg per week over the next 6 weeks. Although several studies have established normal systolic values for full-term infants, data in low birthweight and very low birthweight infants are still limited (Table 1). Hypertension is defined as persistent blood pressure values more than 2 standard deviations above normal values for age and weight.
The reported incidence of neonatal hypertension varies from 0.7% to 3%. This range may be related in part to differences in surveillance, referral patterns, treatment programs, at-risk infants, and to arbitrary diagnoses based on limited normative standards. Nonetheless, a significant fraction of hypertension seen in the pediatric population occurs in the infant, usually in the neonatal intensive care unit.
CAUSES OF HYPERTENSION
The causes of hypertension are listed in Table 2. Although the list of diagnoses has become quite lengthy, a limited number of conditions (in bold type) dominate the clinical picture. These include renal artery thrombosis, coarctation of the aorta, acute renal failure, and chronic lung disease. Renal artery thrombosis, which may occur spontaneously or in association with hypovolemia, closure of a patent ductus arteriosus, coagulopathy or an extrinsic mass, is usually observed in connection with use of umbilical artery catheters.2 Thrombi may form on these catheters and cause embolization at other locations, such as the renal arteries. Renal artery thrombosis appears to be more commonly associated with catheters with tips above the origin of the renal arteries; however, low-placed catheters may also be associated with emboli. The incidence of catheterrelated thrombosis appears to be related to duration of catheterization, presence or absence of heparinization, type of catheter, and local trauma. Although hypertension may result from renal artery thrombosis, not all vascular occlusions are clinically apparent. Although data are insufficient, a significant number of infants with catheters may have silent renal artery thromboses and be at increased risk of renal atrophy or later onset hypertension. The most common other vascular cause of hypertension in neonates is coarctation of the aorta. Although a variety of renal parenchymal diseases, such as polycystic disease or obstructive uropathy, may cause neonatal hypertension, the most common is acute renal failure, a problem often seen in intensive care nurseries and associated with hypertension in 10% to 30% of cases.
Upper Limits of Normal Readings for Mean Arterial Pressure in the Newborn
There are numerous miscellaneous causes of hypertension, including increased intracranial pressure, fluid and electrolyte overload - especially from occult intake of sodium - and the use of drugs, such as corticosteroids and theophylline. A common cause of infant hypertension is chronic lung disease. Indeed approximately 40% of patients with bronchopulmonary dysplasia have hypertension.1' Although these patients may also be receiving corticosteroids and theophylline, chronic lung disease itself may be associated with increased plasma renin activity, catecholamine secretion, and nephrocalcinosis. Acute airway occlusion may cause a rapid but reversible rise in blood pressure.
Hypertension due to renal tumors or endocrine abnormalities is rare, as is essential hypertension. Persistent hypertension in the neonate is usually related to a secondary etiology.
CLINICAL SIGNS AND SYMPTOMS
The signs and symptoms of hypertension are listed in Table 3. As many as 50%> of hypertensive infants detected by routine blood pressure surveillance are completely asymptomatic or only have electrocardiographic or echocardiographic evidence of left ventricular hypertrophy.
Cardiorespiratory symptoms, which may include cyanosis, cardiomegaly, or trank congestive failure, usually resolve both clinically and on echocardiographic examination with control of blood pressure. Neurologic symptoms include lethargy, coma, seizures, intracranial edema, facial nerve palsy, and retinopathy.10 Changes in systemic arterial pressure may be associated with cerebral hemorrhages, which are commonly seen in very low birthweight infants and may contribute to an abnormal neurologic status. Although many factors may contribute to these hemorrhages, acute elevations in systemic blood pressure due to acute volume changes, infant handling, drugs, and stress may play a role. Reported observations in both animals and humans appear to support this somewhat controversial hypothesis.11,12
Etiology of Hypertension in the Neonate*
Other clinical findings in hypertensive infants include patent ductus arteriosus, failure to thrive, vasomotor instability, sodium wasting, renal enlargement, and absent femoral pulses.
The age of hypertension onset may be a clue to etiology. Hypertension due to renal artery or aortic thrombosis usually occurs in the first week or two of life. Hypertension due to patent ductus appears soon after closure; whereas bronchopulmonary dysplasia hypertension develops weeks to months after birth, and is often diagnosed in the outpatient setting.
The evaluation of hypertension is initiated only after persistent blood pressure elevation is confirmed with repeated, accurate measurements in a quiet, resting infant. Initial screening studies include a urinalysis, urine culture, blood urea nitrogen, serum creatinine, serum electrolytes, and plasma renin activity. The need for subsequent studies depends on initial laboratory results and clinical indications. Extensive tests may be costly, invasive, and unwarranted if the diagnosis can be achieved more simply. However, a sensible attempt should be made to determine the etiology of hypertension, as both treatment and prognosis are influenced by the cause. Figure shows an algorithm that may be helpful.18
Although hematuria, proteinuria, azotemia, and elevated plasma renin activity are commonly seen with renal artery thrombosis, these findings may be absent. Conversely, transient hematuria and proteinuria are not uncommon in sick neonates, and elevated plasma renin activity may be caused by other conditions, such as renal failure, hypovolemia, and respiratory distress syndrome. Ultrasonography is useful in detecting aortic thrombosis, renal calculi, genitourinary tract obstruction, renal cystic disease, and renal and adrenal masses. The usefulness of this technique is clearly related to the skill and expetience of the ultrasonographer.
We initially used angiography in the evaluation of renovascular hypertension but now do so infrequently because of its invasiveness and potential side effects and because scintigraphy often provides adequate information to establish the diagnosis. Radioisotopic evaluation can be used with technetium 99 DTPA, p 131I or p 123I iodohippurate, or technetium 99 glucoheptonate. Subtle differences in function between kidneys can be detected using kinetic models in which the abnormal kidney will display a decreased effective renal plasma flow, decreased urine flow rate, and increased isotope concentration when compared with the contralateral kidney.2 Radioisotopic studies are also useful in the subsequent follow-up of renal size and function.
Clinical Manifestations of Neonatal Hypertension
In summary, the evaluation of a hypertensive infant should include an initial history, physical examination, and baseline laboratory data. Infectious, neurologic, iatrogenic, and drug causes are easily ruled out. Abdominal masses may be evaluated with ultrasonography or radiologic studies. Endocrine etiologies are pursued it there are clinical or laboratory indications. Finally, evaluation oí renal parenchymal or vascular causes requires ultrasonography, renal scintigraphy, and occasionally intravenous pyelography or angiography.
MANAGEMENT OF THE HYPERTENSIVE NEONATE
Patients with hypertension due to renal artery or aortic thrombosis usually respond well to medical management and rarely require surgical intervention, such as nephrectomy or embolectomy. In general, surgery is associated with increased mortality and morbidity with no improvement in renal salvage.'4 Surgery may be indicated when vigorous attempts at medical management have failed or when there is massive aortic occlusion with hypotension and anuria; although conservative management may be effective even with anuria.15 Finally, the successful use of anticoagulants, such as streptokinase, urokinase, or tissue plasminogen activator, has been reported. However, no controlled studies show superiority of any of these therapies over conventional antihypertensive care. 16
Figure. Evaluation of hypertension in newborns
The treatment of neonatal hypertension is similar to that in older children and adolescents. Single drug therapy is often effective. Drug dosages are increased until blood pressure is controlled or side effects require addition of other drugs. Mild hypertension is usually treated with diuretics or a vasodilator, such as hydralazine. Some asymptomatic patients may simply be observed. Moderate to severe hypertension may be treated with hydralazine alone or in combination with a diuretic or β-blocker. Captopril is often effective in low dosages, starting at 0.05 mg/kg/dose. Indeed, profound hypotension and renal failure have been reported,17 often several weeks after blood pressure has come under control, when dosages recommended for older children and adults have been used in neonates. Captopril is contraindicated in infants with bilateral renovascular disease or unilateral vascular disease in a solitary kidney. For patients with severe hypertension, graded dosages of diazoxide or, preferably, carefully monitored intravenous nitroprusside may be needed. Blood pressure, once controlled, may respond to less potent antihypertensive agents. Precipitous drops in blood pressure must be avoided to prevent cortical ischemia.
In our experience, blood pressure can usually be controlled in 1 to 7 days. In patients with renal artery thrombosis, antihypertensive medications may be tapered once blood pressure has been controlled tor 4 to 8 weeks. For most patients medication therapy for hypertension is temporary.
Patients with hypertension of different etiologies will often respond to correction of the underlying problem. Thus, correction of obstructive uropathy, tumor removal, treatment of infection, and reduction in salt intake in a volume-overloaded patient will usually relieve hypertension. Children with bronchopulmonary dysplasia often show improvement in hypertension with improvement in pulmonary function or decreases in adjunct medications, such as theophylline and corticosteroids.
The prognosis for neonatal hypertension has improved vastly with the availability of new and potent antihypertensive agents, increased skill in management, and early recognition of elevated blood pressure. Different etiologies may also contribute to an improved prognosis. For example, renal artery thrombosis carries a much better prognosis than does hypoplastic aorta, perhaps related to recanal ization of the thrombosed vessel. Our experience in the long-term follow-up of such infants is encouraging. Most remain normotensive off medications and tend to have normal renal function even though morphologic and functional abnormalities in the affected kidney persist.18 Whether these children are at risk of later developing hypertension, proteinuria, and renal insufficiency remains unclear.
Table 1 is adapted from Stork EK, Carlo WA, Kliegman RM, et ah Pediatr Res 1984; 321A. The figure is adapted from Ingelfinger.13
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2. Adelman RD. Metten D, Vogel J. et al: Nonsurgical management of renovascular hypertension in the neonate. Pediatrics 1978; 62:71-76.
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10. Skalina ME, Annable WL, Kliegman RM, et al: Hypertensive retinopathy in the newborn infant. J Pediatr 1983; 103:781-786.
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13. Ingelfinger JR: Pediatric Hypertension. Philadelphia. Saunders, 1982, pp 229-240.
14. Mover JD, Rao CN, Widrich WC. et al: Conservative management of renal artery embolus. J Urol 1973; 109:138-143.
15. Malin SW, Baumgart S, Rosenberg HK. et al: Nonsurgical management of obstructive aortic thrombosis complicated by renovasculat hypertension in the neonate. 1 Pediatr 1985; 106:630-634.
16. Schmidt B, Andrew M: Neonatal thrombotic disease: Prevention, diagnosis and treatment. J Pediatr 1988; 113:407-410.
17. Mirkin BL, Newman TJ: Efficacy and safety of captopril in the treatment of severe childhood hypertension: Report of the International Collaborative Study Group. Pediatrics 1985; 75:1091-1100.
18. Adelman RD: Long-term follow-up of neonatal renovascular hypertension, Pediatric Nephrology 1987; 1:36-41.
Upper Limits of Normal Readings for Mean Arterial Pressure in the Newborn
Etiology of Hypertension in the Neonate*
Clinical Manifestations of Neonatal Hypertension